Compassionate Use Program to Access Trametinib and Dabrafenib for Patients With BRAF Mutation-positive Metastatic Melanoma

NCT04489433 | Unknown

• 1 other identifier: CDRB436B2005CM
• Study Type: expanded_access
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this Cohort Treatment Plan is to allow access to trametinib (monotherapy or in combination) and dabrafenib (monotherapy or in combination) for eligible patients diagnosed with metastatic melanoma BRAF mutation-positive.

Conditions

Melanoma

Keywords

Metastatic melanoma; Melanoma; Stage IV melanoma; Cutaneous; Mucosal; Ocular; Dabrafenib; Trametinib; DRB436; TMT212; Compassionate Use; Cohort; Expanded access

Interventions

Dabrafenib DRUG

If administration of dabrafenib is interrupted or permanently discontinued, administration of trametinib may continue.

Trametinib DRUG

If administration of trametinib is interrupted or permanently discontinued, administration of dabrafenib may be continued.

Dabrafenib and Trametinib DRUG

The starting dose of the combination treatment will be administered as follows: * Dabrafenib, 150 mg, twice daily (BID); * Trametinib, 2.0 mg, once daily (QD)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has or is willing to give consent to the Treating Physician in accordance with the local regulatory requirements, with age at the time of consent ≥18 years.
• Has confirmed BRAF V600 or other BRAF activating mutation-positive metastatic melanoma. Histologically Stage IIIC (unresectable) or Stage IV (metastatic) cutaneous melanoma with confirmed BRAF V600E/K positive mutation.
• All clinical trials that the patient might qualify for have been ruled out.
• Is receiving care at a clinical site with a Treating Physician who has experience with administering investigational agents for the end-stage melanoma population, or the patient is willing and/or able to travel to a site and receive treatment under the guidance of physician with this experience. NOTE: The latter option would require the patient being evaluated in advance by the Treating Physician at the experienced site and his/her agreement to assume responsibility for the care of the patient.
• Is able to retain oral medication and swallow tablets/capsules (appropriate exceptions allowed for patients who are unable to swallow tablets/capsules - this is subject to availability of alternative (liquid) oral formulations).
• Does not require treatment with any (other) anti-cancer medication (exceptions might be allowed and are subject to individual evaluation).
• For patients with active brain metastases: the patient does not require or is ineligible for immediate local treatment.
• Is not eligible for participation in any of the IMP's ongoing clinical trials or has recently completed a clinical trial that has been terminated and, after considering other options (e.g., trial extensions, amendments, etc.), the clinical team has determined that treatment is necessary and there are no other feasible alternatives for the patient.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 3 (or equivalent) and is in stable clinical condition. NOTE: patient in rapidly deteriorating clinical condition prior to start of therapy should not be considered for this program.
• Does not require treatment with prohibited concomitant medications
• Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (HCG) pregnancy test performed within 14 days prior to starting dabrafenib and trametinib treatment. Subjects with a positive pregnancy test result must be excluded from the program. Subjects with a negative pregnancy test result must agree to use an effective contraception method as described below throughout the treatment period and for a total of 4 months following the last dose of treatment.
• Contraceptive Methods for Females of Childbearing Potential:
• An intrauterine device with a documented failure rate of less than 1% per year
• Vasectomized partner who is sterile prior to the female patient's entry into the Compassionate Use program, and this male is the sole sexual partner for that female.
• Complete abstinence from sexual intercourse for 14 days prior to first dose of treatment, through the dosing period, and for at least 4 months after the last dose of treatment. Abstinence is only acceptable when in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

You may not qualify if:

• Patients eligible for this Treatment Plan must not meet any of the following criteria:
• Uveal or mucosal melanoma.
• Female who is pregnant or nursing (patient must discontinue nursing in order to enroll in the program).
• Patients who have any lab abnormalities or AE/SAEs greater than Grade 3 (CTCAE v5.0)
• Concurrent treatment with other systemic anti-cancer therapies is not allowed, with the exception of whole brain radiation and brain radiosurgery. Patients who are currently being treated with another systemic anti-cancer therapy (e.g., chemotherapy, immune, biologic, or targeted therapy) must discontinue use prior to initiation of treatment with trametinib and dabrafenib. NOTE: Radiation skin injury has been reported with concurrent use of dabrafenib and radiation. All AEs/SAEs related to WBRT (whole brain radiation) or brain radiosurgery are required to resolve to Grade 1 or less (CTCAE v5.0) prior to start of the Managed Access Program treatment.
• Patients who have received prior therapy with a BRAF inhibitor other than dabrafenib.
• NOTE: Consideration may be given to those patients who have either (1) received prior BRAF therapy and there is disease progression in the CNS only or (2) discontinued prior BRAF therapy due to an adverse event that is not likely to recur in response to treatment with Dabrafenib
• Presence of any malignancy with confirmed activating RAS mutation. NOTE: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
• Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib or dabrafenib, or excipients or to dimethyl sulfoxide (DMSO).
• Any medical conditions or physical examination or clinical laboratory findings which would put the patient at high risk for an adverse outcome.
• Current evidence / risk of retinal vein occlusion (RVO) or central serous retinopathy.
• Current evidence of cardiovascular risk including any of the following:
• LVEF\<LLN
• A QT interval corrected for heart rate using the Bazett's formula greater or equal to 480 msec;
• Clinically significant uncontrolled arrhythmias

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Melanoma

Interventions

dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: expanded access
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2020
• First Posted: July 28, 2020
• Last Updated: December 18, 2025

Record last verified: 2025-12